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Dopamine from the Brain Promotes Spinal Motor Neuron Regeneration

1. Dev Cell. 2013 June 10. pii: S1534-5807(13)00241-4. doi: 10.1016/j.devcel.2013.04.012. Dopamine from the Brain Promotes Spinal Motor Neuron Generation during Development and Adult Regeneration. Reimer MM, Norris A, Ohnmacht J, Patani R, Zhong Z, Dias TB, Kuscha V, Scott AL, Chen YC, Rozov S, Frazer SL, Wyatt C, Higashijima SI, Patton EE, Panula P, Chandran S, Becker T, Becker CG. Centre for Neuroregeneration, School of Biomedical Sciences, The Chancellor's Building, University of Edinburgh, Edinburgh EH16 4SB, UK. Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal.

This pathway can be pharmacologically stimulated to promote regeneration of motor neurons in an adult vertebrate.

Thus, our results demonstrate that descending axons regulate the generation of spinal neurons during development and adult regeneration and identify dopamine signaling as a powerful regulator of spinal neurogenesis.

Members of the forum will probably mock this study ("lol zebrafish!?!?!?"). Filter out the noise. These findings are very significant.